Differential regulation of TLR-dependent MyD88 and TRIF signaling pathways by free zinc ions.
J Immunol
; 191(4): 1808-17, 2013 Aug 15.
Article
em En
| MEDLINE
| ID: mdl-23863901
ABSTRACT
Zinc signals are utilized by several immune cell receptors. One is TLR4, which causes an increase of free zinc ions (Zn(2+)) that is required for the MyD88-dependent expression of inflammatory cytokines. This study investigates the role of Zn(2+) on Toll/IL-1R domain-containing adapter inducing IFN-ß (TRIF)-dependent signals, the other major intracellular pathway activated by TLR4. Chelation of Zn(2+) with the membrane-permeable chelator N,N,N',N'-Tetrakis(2-pyridylmethyl)ethylenediamine augmented TLR4-mediated production of IFN-ß and subsequent synthesis of inducible NO synthase and production of NO. The effect is based on Zn(2+) acting as a negative regulator of the TRIF pathway via reducing IFN regulatory factor 3 activation. This was also observed with TLR3, the only TLR that signals exclusively via TRIF, but not MyD88, and does not trigger a zinc signal. In contrast, IFN-γ-induced NO production was unaffected by N,N,N',N'-Tetrakis(2-pyridylmethyl)ethylenediamine. Taken together, Zn(2+) is specifically involved in TLR signaling, where it differentially regulates MyD88 and TRIF signaling via a zinc signal or via basal Zn(2+) levels, respectively.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Zinco
/
Transdução de Sinais
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Proteínas Adaptadoras de Transporte Vesicular
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Receptor 4 Toll-Like
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Fator 88 de Diferenciação Mieloide
Limite:
Animals
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Alemanha